Objective: To investigate the therapeutic effect of integrin receptor antagonist cilengitide on intestinal fibrosis in rats. Methods: Twenty-one SD rats were equally randomized into control group, model group and cilengitide treatment group, Intestinal fibrosis model was induced in rats in the latter two groups by continuous intracolonically injection with increasing doses of trinitrobenzene sulfonic acid (TNBS) in 45% ethanol solution for 6 weeks, and rats in cilengitide treatment group simultaneously received daily intraperitoneal injection of cilengitide, while those in the other two groups were given normal saline of the same volume in the same administration manner. During the experimental period, the general conditions were observed and the changes in body weight were recorded in each group of rats. The rat colonic tissue specimens were harvested after 6 weeks, the intestinal inflammation and collagen deposition were examined and the levels of TGF-β1, collagen type Iα1 mRNA and collagen type I protein in colonic tissues were measured. Results: Except for control group, rats in the other two groups showed poor general conditions and an initial decrease and subsequent increase in body weight, but the general conditions in rats in cilengitide treatment group were better than those in model group, and the amplitude of later body weight gain in rats in cilengitide treatment group was significantly greater than that in model group (P<0.05); rats in these two groups had evident chronic inflammation and deposition of collagen fibers in the colonic tissues, but the histopathological score and collagen fiber content in cilengitide treatment group were significantly lower than those in model group (both P<0.05). Compared with control group, the colonic levels of total TGF-β1 and activated TGF-β1, and levels of collagen type Iα1 mRNA and collagen type I protein were significantly increased in rats in the other two groups, but the levels of activated TGF-β1, collagen type Iα1 mRNA and collagen type I protein in cilengitide treatment group were significantly lower than those in model group (all P<0.05). Conclusion: Cilengitide can attenuate intestinal fibrosis through inhibiting TGF-β1 activation resulting from its integrin receptor antagonizing effect.